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Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy

Abstract

A number of emerging studies in field of immune metabolism have indicated that cellular metabolic reprograming serves as a major administrator in maintaining the viability and functions of both tumor cells and immune cells. As one of the most important immunosuppressive cells in tumor stroma, myeloid-derived suppressor cells (MDSCs) dynamically orchestrate their metabolic pathways in response to the complicated tumor microenvironment (TME), a process that consequently limits the therapeutic effectiveness of anti-cancer treatment modalities. In this context, the metabolic vulnerabilities of MDSCs could be exploited as a novel immune metabolic checkpoint upon which to intervene for promoting the efficacy of immunotherapy. Here, we have discussed about recent studies highlighting the important roles of the metabolic reprograming and the core molecular pathways involved in tumor-infiltrating MDSCs. In addition, we have also summarized the state-of-the-art strategies that are currently being employed to target MDSC metabolism and improve the efficacy of antineoplastic immunotherapy.

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Fig. 1: Metabolic interactions of MDSCs with TME.
Fig. 2: An overview of cellular metabolic reprograming in MDSCs.
Fig. 3: An overview of key metabolic pathways and their associated signaling events in MDSCs during metabolic alternations.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 82071749).

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QL designed and drafted the manuscript; MX designed and edited the manuscript.

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Correspondence to Ming Xiang.

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The authors declare no competing interests.

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Li, Q., Xiang, M. Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy. Acta Pharmacol Sin (2021). https://doi.org/10.1038/s41401-021-00776-4

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Keywords

  • myeloid-derived suppressor cells
  • tumor microenvironment
  • metabolic reprograming
  • cancer immunotherapy
  • metabolic intervention

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